19-49460909-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_153329.4(ALDH16A1):c.577+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00908 in 1,611,740 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0094 (96 hom.)
• Consequence: ALDH16A1 NM_153329.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.11

Genes affected

ALDH16A1 (HGNC:28114): (aldehyde dehydrogenase 16 family member A1) This gene encodes a member of the aldehyde dehydrogenase superfamily. The family members act on aldehyde substrates and use nicotinamide adenine dinucleotide phosphate (NADP) as a cofactor. This gene is conserved in chimpanzee, dog, cow, mouse, rat, and zebrafish. The protein encoded by this gene interacts with maspardin, a protein that when truncated is responsible for Mast syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 19-49460909-G-A is Benign according to our data. Variant chr19-49460909-G-A is described in ClinVar as [Benign]. Clinvar id is 777914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH16A1	NM_153329.4	c.577+10G>A		intron_variant		ENST00000293350.9
ALDH16A1	NM_001145396.2	c.577+10G>A		intron_variant
ALDH16A1	XM_011526441.1	c.490+10G>A		intron_variant
ALDH16A1	XM_047438163.1	c.490+10G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH16A1	ENST00000293350.9	c.577+10G>A		intron_variant		1	NM_153329.4	P1

Frequencies

GnomAD3 genomes AF: 0.00603 AC: 918 AN: 152170 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00539 AC: 1352 AN: 250890 Hom.: 13 AF XY: 0.00533 AC XY: 724 AN XY: 135790

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.00399

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00968

Gnomad OTH exome AF: 0.00604

GnomAD4 exome AF: 0.00939 AC: 13710 AN: 1459452 Hom.: 96 Cov.: 31 AF XY: 0.00893 AC XY: 6487 AN XY: 726166

Gnomad4 AFR exome AF: 0.00129

Gnomad4 AMR exome AF: 0.00396

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.00169

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.00853

GnomAD4 genome AF: 0.00602 AC: 917 AN: 152288 Hom.: 8 Cov.: 31 AF XY: 0.00544 AC XY: 405 AN XY: 74444

Gnomad4 AFR AF: 0.00202

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00703 Hom.: 2

Bravo AF: 0.00609

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	8.8
Dann	Benign	0.72
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146957921; hg19: chr19-49964166;